chr14-20060162-A-G

Variant names:

• chr14-20060162-A-G
• rs1958716
• NM_001004717.1:c.118A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004717.1(OR4L1):​c.118A>G​(p.Met40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,597,686 control chromosomes in the GnomAD database, including 156,739 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15310 hom., cov: 31)
  • Exomes 𝑓: 0.43 (141429 hom.)
• Consequence: OR4L1 NM_001004717.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.57
• Publications: 30 publications found

Genes affected

OR4L1 (HGNC:15356): (olfactory receptor family 4 subfamily L member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1081136E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4L1	NM_001004717.1	c.118A>G	p.Met40Val	missense_variant	Exon 1 of 1	ENST00000315683.1	NP_001004717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4L1	ENST00000315683.1	c.118A>G	p.Met40Val	missense_variant	Exon 1 of 1	6	NM_001004717.1	ENSP00000319217.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66976 AN: 151676 Hom.: 15277 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.469 AC: 114711 AN: 244498 AF XY: 0.473

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.433 AC: 625908 AN: 1445892 Hom.: 141429 Cov.: 29 AF XY: 0.440 AC XY: 316406 AN XY: 719502

African (AFR) AF: 0.488 AC: 16109 AN: 33022

American (AMR) AF: 0.592 AC: 25613 AN: 43238

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 9681 AN: 25700

East Asian (EAS) AF: 0.556 AC: 21921 AN: 39450

South Asian (SAS) AF: 0.689 AC: 57993 AN: 84190

European-Finnish (FIN) AF: 0.326 AC: 17348 AN: 53166

Middle Eastern (MID) AF: 0.504 AC: 2873 AN: 5702

European-Non Finnish (NFE) AF: 0.406 AC: 447209 AN: 1101708

Other (OTH) AF: 0.455 AC: 27161 AN: 59716

GnomAD4 genome AF: 0.442 AC: 67066 AN: 151794 Hom.: 15310 Cov.: 31 AF XY: 0.445 AC XY: 32972 AN XY: 74156

African (AFR) AF: 0.495 AC: 20469 AN: 41376

American (AMR) AF: 0.504 AC: 7670 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2927 AN: 5136

South Asian (SAS) AF: 0.685 AC: 3294 AN: 4808

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26764 AN: 67922

Other (OTH) AF: 0.430 AC: 905 AN: 2104

Alfa AF: 0.422 Hom.: 53373

Bravo AF: 0.453

TwinsUK AF: 0.413 AC: 1532

ALSPAC AF: 0.421 AC: 1624

ESP6500AA AF: 0.489 AC: 2154

ESP6500EA AF: 0.403 AC: 3465

ExAC AF: 0.471 AC: 57194

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.057
DANN	Benign	0.61
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.89	N
PhyloP100		-6.6
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.046
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.011
ClinPred		0.018	T
GERP RS		-5.8
PromoterAI		-0.013	Neutral
Varity_R		0.052
gMVP		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1958716; hg19: chr14-20528321; COSMIC: COSV107326170;